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Lecture Notes - Endocrinology > Female reproductive physiology, amenorrhoea and premature ovarian failure > Flashcards

Female reproductive physiology, amenorrhoea and premature ovarian failure Flashcards

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1
Q

What are the 2 phases of the menstrual cycle

A

Follicular (onset of mess and ends on the day of LH surge

Luteal (begins on the day of the LH surge and ends at the onset of the next menses

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2
Q

How long is the average adult menstrual cycle

A

28 days - 15 days in each phase

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3
Q

What is the first day of the cycle

A

the first day of menses

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4
Q

What are longer menstrual cycles normally associated with

A

anovulation

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5
Q

In terms of oocytes, what happens during each normal menstrual cycle

A

a single mature oocyte is released from a pool of hundred of thousands of primordial oocytes

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6
Q

What hormone levels are low during the follicular stage

A

serum oestradiol and progesterone

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7
Q

What does a low serum estradiol and progesterone result in

A

Negative feedback which results in increased GnRH pulse frequency

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8
Q

What is the effect of an increased GnRH pulse frequency

A

Increases serum FSH levels and LH pulse frequency

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9
Q

What does the increase in FSH stimulate

A

the recruitment and growth of a cohort of ovarian follicles

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10
Q

What do ovarian follicles consist of

A

oocytes surrounded by granulosa cells and theca cells

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11
Q

What enzyme does FSH stimulate

A

Aromatase (in the granulosa cells of the dominant follicle)

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12
Q

What is the function of aromatase

A

It converts androgens (synthesised in the theca cells) to oestrogen

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13
Q

What does the increase in estradiol production initially do

A

suppresses serum FSH and LH levels

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14
Q

What else plays a role in suppressing FSH

A

Serum inhibin B

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15
Q

What happens to the rest of the growing follicles

A

They undergo atresia after a single dominant follicle is selected

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16
Q

How does the LH surge arise

A

The negative feedback effect of ovarian steroids (particularly oestradiol) switches to a positive feedback effect

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17
Q

What is the LH surge associated with

A

an increased frequency of FnRH secretion and enhanced pituitary sensitivity to GnRH

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18
Q

What happens to estradiol secretion just before ovulation

A

It reaches a peak and then falls

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19
Q

How long does it take for the oocyte to be released following the LH surge

A

36 hours

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20
Q

What do the granulosa cells begin to produce and what do they develop into post oocyte release

A

Progesterone

Corpus luteum

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21
Q

What starts to rise towards the end of the luteal phase and why

A

FSH starts to rise to stimulate the development of the next follicle usually in the contralateral ovary.
This occurs due to the progesterone and oestrogen levels falling

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22
Q

Describe the levels of Inhibin A during the menstrual cycle

A

Low in the follicular phase and increased in the luteal phase

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23
Q

What happens to the corpus luteum and progesterone production if the oocyte becomes fertilised

A

The corpus luteum is maintained and progesterone production is also maintained

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24
Q

What is the effect of the serum estradiol concentrations during the follicular phase on the endometrium

A

Proliferation of the uterine endometrium and glandular growth occurs

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25
What happens to the arterioles supplying the endometrium as the function of the corpus luteum declines
The arterioles undergo vasospasm (caused by locally synthesised protaglandins) causing ischaemic necrosis, endometrial desquamation (shedding) and bleeding
26
What is the principal and most potent oestrogen secreted by the ovary
Oestradiol
27
What do oestrogens promote
Development of secondary sexual characteristics (breast development etc.) cause uterine growth play an important role in regulation of menstrual cycle
28
How do oestrogens act
They bind to a nuclear receptor which binds to specific DNA sequences and regulates the transcription of various genes
29
What is the principle hormone secreted by the corpus luteum
Progesterone
30
What is progesterone responsible for
Pro gestational effects - including induction of secretory activity in the endometrium in preparation for the implantaion of a fertilised egg Inhibition of uterine contractions increased viscosity of cervical mucus glandular development of the breasts
31
Describe the change in temperature during the menstrual cycle
It increased by 0.3-0.5 degrees after ovulation and persists during the luteal phase and returns to normal after the onset of menses
32
What is inhibit
a glycoprotein consisting of two disulphide-linked subunits, alpha and beta
33
Why are there two forms of inhibit
The beta subunit can exist in 2 forms
34
Where is inhibin B secreted and what is its function
secreted by the follicle and inhibits the release of FSH from he pituitary
35
Where is inhibin A secreted and what is its function
Secreted by the Corpus luteum of the last cycle | levels are low in follicular phase and increased i the luteal phase
36
What is amenorrhoea
the absence of menstrual periods in a woman during her reproductive year It can be primary or secondary
37
What is primary amenorrhoea
The absence of menstrual periods by age 14 in a girls without breast development or by age 16 in a girl with breast development
38
What is secondary amenorrhoea
The absence of menstrual periods for more than 3 months in a woman who has previously had an established menstrual cycle
39
What has a higher incidence, primary or secondary amenorrhoea
Secondary
40
What are some of the causes of amenorrhoea
Functional - street, weight loss, excessive exercise, eating disorders Pituitary and hypothalamic tumours - adenomas, craniopharyngiomas, haemochromatosis Hyperprolactinomas - cause pituitary stalk compression Kallmann's syndrome Premature ovarian failure - chromosomal abnormalities, autoimmune, iatrogenic, Uterine and vaginal outflow - congenital anatomical abnormalities Thyroid dysfunction - Hypothyroidism or thyrotoxicosis Hyperandrogenism- congenital adrenal hyperplasia, PCOS Imperforate hymen transverse vaginal septum between the cervix and the hymenal ring (prevents the egress o menses)
41
Amenorrhoea may be due to a defect at what levels
``` Hypothalamus Pituitary Ovaries Uterus Vaginal outflow tract ```
42
What is functional hypothalamic amenorrhoea characterised by
abnormal hypothalamic GnRH secretion, resulting in decreased gonadotrophin pulsations
43
What might pituitary/ hypothalamic tumours cause
hypogonadotrophic hypogonadism and amenorrhoea
44
What does hypoerprolactinaemia do
It can interrupt the transport of dopamine to the anterior pituitary which normally exerts an inhibitory effect on prolactin secretion
45
What is Kallmann's syndrome
Patients have congenital GnRH deficiency associated with anosmia
46
How can congenital GnRH be inherited
Autosomal dominant autosomal recessive or X linked
47
What is premature ovarian failure
Primary hypogonadism (lack of folliculogenesis and ovarian oestrogen production) before the age of 40
48
What do the largest number of patients with primary amenorrhoea and ovarian failure have
turner's syndrome
49
What might acquired ovarian faker be cdue to
chemotherapy radiotherapy Autoimmune
50
What is Mullein agenesis characterised by
congenital absence of the vagina with variable uterine development
51
What is the most common cause of primary amenorrhoea with excess androgen production
congenital adrenal hypoerplasia (CAH)
52
What does PCOS have a strong association with
insulin resistnace
53
What are the features of Turner's syndrome
lack of secondary sexual characteristics short stature widely spaced nipples low posterior hairline High arched palate, wide carrying angle, short 4th and 5th metacarpals Cardio - congenital lymphoedema, aortic dissection, cortication of the aorta, hypertension GI: angiodysplasia, coeliac disease Renal: horseshoe kidneys, abnormal vascular supply Endocrine: increased risk of hypothyroidism and Diabetes mellitus
54
What are some areas to ask the patient about when presenting with amenorrhoea
Change in weight, stress, excessive dieting, exercise or illness Drugs - contraceptive pill Hypothalamic-pituitary disease e.g. headaches, visual field defects, fatigue, polyuria or polydipsia Galactorrhoea (suggestive of hyperprolactinaemia Symptoms of oestrogen deficiency e.g. hot flush, dry vagina, poor sleep or reduced libido Hirsutism, acne or deepening of the voice Hx of lower abdominal pain at the time of expected menses History of dilatation and curettage or endometritis that might have caused scarring
55
What should the physical exam for amenorrhoea include
Tanner staging for pubertal development Measurements of height, weight and BMI signs of associated underlying causes e.g. visual field defect, imperforate hymen, thyroid problems
56
What is a sign of insulin resistance that patients with PCOS may have
Acanthosis nigricans (darkened areas of the skin) often in the armpits
57
What are some of the initial tests for amenorrhoea
``` Pregnancy test (serum or urine human chorionic gonadotrophin) Pelvic imaging (US or MRI) Serum FSH serum prolactin serum TSH and T4 Serum androgens ```
58
Why are serum FSH levels tested in amenorrhoea
elevated in premature ovarian failure due to reduced inhibition due to ovarian oestradiol and inhibin
59
What should patients have done if they have high FSH or are suggestive of primary ovarian failure
Karyotype to look for chromosomal abnormalities e.g. Turner's
60
When is a hypothalamic -pituitary MRI indicated
In women with hypogonadotrophic hypogonadism and no clear explanation Those with visual field defects, headaches or any other signs of hypothalamic - pituitary dysfunction
61
What should be included in the differential diagnosis for patients with hyperandrogenism
PCOS CAH androgen-secreting tumours
62
What should also be tested for if a patient is suspected to have Turner's syndrome
``` Echocardiogram (congenital heart disease / aortic aneurysm) Renal US (renal anomalies) Thyroid function tests (a lot develop thyroid disease) ```
63
Why should women with unexplained premature ovarian failure be screened for permutation in the FMR1 gene.
There is a risk that a patient with an FMR1 mutation would have a child with mental retardation and also has a link to fragile X syndrome
64
How are the majority of women with prolactinomas successfully treated
Dopamine agonist
65
What should patients with irreversible gonadotrophin deficiency receive
Oestrogen replacement therapy and progesterone if they have a uterus
66
What should be started in girls with primary amenorrhoea and delayed puberty
Oral ethinylestradiol at a low dose to promote breast development and adult body habitus Dose is gradually increased Cyclical oral progesterone is added with the onset of breakthrough bleeding
67
What can premature initiation of progesterone therapy cause
compromise ultimate breast growth
68
What is required for the prevention of osteoporosis and coronary heart disease
Oestrogen-progestin replacement therapy
69
What might adult women with premature ovarian failure be treated with
100ug of transdermal estradiol daily
70
What must be performed in patients with Y chromosome material
gonadectomy - to prevent the development of gonadal tumours

Lecture Notes - Endocrinology (40 decks)

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